Ultiva

"The US Food and Drug Administration (FDA) has approved diclofenac sodium injection (Dyloject, Hospira Inc), a proprietary nonsteroidal anti-inflammatory drug (NSAID) for the treatment of mild to moderate pain, and for the management of mod"...

Ultiva is for intravenous (IV) use only and is administered under a physician's supervision. Dose is determined by weight of the patient. Your breathing and other vital signs will be constantly monitored while you are treated with this drug. Ultiva may interact with MAO inhibitors, drugs for sleep, sedatives, tranquilizers, anti-anxiety drugs, narcotic pain relievers, psychiatric medicines, anti-seizure drugs, muscle relaxants, or antihistamines. Check the labels on all medicines (e.g., cough-and-cold products) because they may contain drowsiness-causing ingredients. Tell your doctor all medications you are taking. Ultiva should be used during pregnancy only if prescribed. It is not known whether this medication passes in breast milk. Consult your doctor before breast-feeding.

Our Ultiva (remifentanil) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Adverse event information is derived from controlled clinical trials that were
conducted in a variety of surgical procedures of varying duration, using a variety
of premedications and other anesthetics, and in patient populations with diverse
characteristics including underlying disease.

Adults: Approximately 2770 adult patients were exposed to ULTIVA (remifentanil) in
controlled clinical trials. The frequencies of adverse events during general
anesthesia with the recommended doses of ULTIVA (remifentanil) are given in Table 3. Each patient
was counted once for each type of adverse event.

Table 3: Adverse Events Reported in 1% of Adult Patients
in General Anesthesia Studies* at the Recommended Doses† of ULTIVA (remifentanil)

Adverse Event

Induction/Maintenance

Postoperative Analgesia

After Discontinuation

ULTIVA
(n = 921)

Alfentanil/ Fentanyl
(n = 466)

ULTIVA
(n = 281)

Morphine
(n = 98)

ULTIVA
(n = 929)

Alfentanil/ Fentanyl
(n = 466)

Nausea

8 ( < 1%)

0

61 (22%)

15 (15%)

339 (36%)

202 (43%)

Hypotension

178 (19%)

30 (6%)

0

0

16 (2%)

9 (2%)

Vomiting

4 ( < 1%)

1 ( < 1%)

22 (8%)

5 (5%)

150 (16%)

91 (20%)

Muscle rigidity

98

(11%)‡ 37

(8%) 7

(2%) 0

2 ( < 1%)

1 ( < 1%)

Bradycardia

62 (7%)

24 (5%)

3 (1%)

3 (3%)

11 (1%)

6 (1%)

Shivering

3 ( < 1%)

0

15 (5%)

9 (9%)

49 (5%)

10 (2%)

Fever

1 ( < 1%)

0

2 ( < 1%)

0

44 (5%)

9 (2%)

Dizziness

0

0

1 ( < 1%)

0

27 (3%)

9 (2%)

Visual disturbance

0

0

0

0

24 (3%)

14 (3%)

Headache

0

0

1 ( < 1%)

1 (1%)

21 (2%)

8 (2%)

Respiratory depression

1 ( < 1%)

0

19 (7%)

4 (4%)

17 (2%)

20 (4%)

Apnea

0

1 ( < 1%)

9 (3%)

2 (2%)

2 ( < 1%)

1 ( < 1%)

Pruritus

2 ( < 1%)

0

7 (2%)

1 (1%)

22 (2%)

7 (2%)

Tachycardia

6 ( < 1%)

7 (2%)

0

0

10 (1%)

8 (2%)

Postoperative pain

0

0

7 (2%)

0

4 ( < 1%)

5 (1%)

Hypertension

10 (1%)

7 (2%)

5 (2%)

3 (3%)

12 (1%)

8 (2%)

Agitation

2 ( < 1%)

0

3 (1%)

1 (1%)

6 ( < 1%)

1 ( < 1%)

Hypoxia

0

0

1 ( < 1%)

0

10 (1%)

7 (2%)

*Does not include adverse events from cardiac
studies or the neonatal study. See Tables 6, 7, and 8 for cardiac information.
† See Table 10 for recommended doses. Not all doses of ULTIVA (remifentanil)
were equipotent to the comparator opioid. Administration of ULTIVA (remifentanil) in
excess of the recommended dose (i.e., doses > 1 and up to 20 mcg/kg)
resulted in a higher incidence of some adverse events: muscle rigidity
(37%), bradycardia (12%), hypertension (4%), and tachycardia (4%).
‡ Included in the muscle rigidity incidence is chest wall rigidity
(5%). The overall muscle rigidity incidence is < 1% when remifentanil
is administered concurrently or after a hypnotic induction agent.

In the elderly population ( > 65 years), the incidence of hypotension is higher,
whereas the incidence of nausea and vomiting is lower.

Table 4: Incidence (%) of Most Common Adverse Events by Gender
in General Anesthesia Studies* at the Recommended Doses† of ULTIVA (remifentanil)

Adverse Event n

Induction/Maintenance

Postoperative Analgesia

After Discontinuation

ULTIVA

Alfentanil/ Fentanyl

ULTIVA

Morphine

ULTIVA

Alfentanil/ Fentanyl

Male 326

Female 595

Male 183

Female 283

Male 85

Female 196

Male 36

Female 62

Male 332

Female 597

Male 183

Female 283

Nausea

2%

< 1%

0

0

12%

26%

8%

19%

22%

45%

30%

52%

Hypotension

29%

14%

7%

6%

0

0

0

0

2%

2%

2%

2%

Vomiting

< 1%

< 1%

0

< 1%

4%

10%

0

8%

5%

22%

8%

27%

Muscle rigidity

17%

7%

14%

4%

6%

1%

0

0

< 1%

< 1%

0

< 1%

*Does not include adverse events from cardiac
studies or the neonatal study.
† See Table 10 for recommended doses. Not all doses of ULTIVA (remifentanil)
were equipotent to the comparator opioid.

The frequencies of adverse events from the clinical studies at the recommended
doses of ULTIVA (remifentanil) in monitored anesthesia care are given in Table 5.

Other Adverse Events in Adult Patients: The frequencies of less commonly
reported adverse clinical events from all controlled general anesthesia and
monitored anesthesia care studies are presented below.

Event frequencies are calculated as the number of patients who were administered
ULTIVA (remifentanil) and reported an event divided by the total number of patients exposed
to ULTIVA (remifentanil) in all controlled studies including cardiac dose-ranging and neurosurgery
studies (n = 1883 general anesthesia, n = 609 monitored anesthesia care).

The frequencies of adverse events from the clinical studies at the recommended
doses of ULTIVA (remifentanil) in cardiac surgery are given in Tables 6, 7, and 8. These tables
represent adverse events collected during discrete phases of cardiac surgery.
Any event should be viewed as temporally associated with drug administration
and the phase indicated should not be perceived as the only time the event might
occur.

Table 6: Adverse Events Reported in 1% of Patients in the
Induction/Intubation and Maintenance Phases of Cardiac Surgery Studies at the
Recommended Doses* of ULTIVA (remifentanil)

Adverse Event

Induction/Intubation

Maintenance

ULTIVA
(n = 227)

Fentanyl
(n = 176)

Sufentanil
(n = 41)

ULTIVA
(n = 227)

Fentanyl
(n = 176)

Sufentanil
(n = 41)

Hypotension

18 (8%)

6 (3%)

7 (17%)

26 (11%)

6 (3%)

1 (2%)

Bradycardia

9 (4%)

5 (3%)

0

3 (1%)

1 ( < 1%)

1 (2%)

Hypertension

3 (1%)

2 (1%)

2 (5%)

8 (4%)

6 (3%)

1 (2%)

Constipation

9 (4%)

1 ( < 1%)

3 (7%)

0

0

1 (2%)

Muscle rigidity

2 ( < 1%)

2 (1%)

0

5 (2%)

8 (5%)

0

Premature ventricular beats

1 ( < 1%)

0

0

3 (1%)

1 ( < 1%)

0

Myocardial ischemia

0

0

0

7 (3%)

8 (5%)

1 (2%)

Atrial fibrillation

0

0

0

7 (3%)

3 (2%)

1 (2%)

Decreased cardiac output

0

0

0

5 (2%)

1 ( < 1%)

1 (2%)

Tachycardia

0

1 ( < 1%)

0

4 (2%)

2 (1%)

0

Coagulation disorder

0

0

0

4 (2%)

0

1 (2%)

Arrhythmia

0

0

0

3 (1%)

0

0

Ventricular fibrillation

0

0

0

3 (1%)

1 ( < 1%)

1 (2%)

Postoperative complication

0

0

0

3 (1%)

0

0

Third degree heart block

0

0

0

2 ( < 1%)

0

1 (2%)

Hemorrhage

0

0

0

2 ( < 1%)

0

1 (2%)

Perioperative complication

0

0

0

2 ( < 1%)

1 ( < 1%)

1 (2%)

Involuntary movement(s)

0

0

0

2 ( < 1%)

3 (2%)

0

Thrombocytopenia

0

0

1 (2%)

0

0

0

Oliguria

0

0

0

0

3 (2%)

0

Anemia

0

0

0

2 ( < 1%)

2 (1%)

0

*See Table 13 for recommended doses.

Table 7: Adverse Events Reported in 1% of Patients in the
ICU Phase of Cardiac Surgery Studies at the Recommended Doses* of ULTIVA (remifentanil)

Adverse Event

ULTIVA
n = 227

Fentanyl
n = 176

Sufentanil
n = 41

Hypertension

14 (6%)

8 (5%)

2 (5%)

Hypotension

12 (5%)

3 (2%)

1 (2%)

Tachycardia

9 (4%)

5 (3%)

0

Shivering

8 (4%)

3 (2%)

1 (2%)

Nausea

8 (4%)

3 (2%)

0

Hemorrhage

4 (2%)

1 ( < 1%)

1 (2%)

Postoperative complication

4 (2%)

5 (3%)

2 (5%)

Agitation

4 (2%)

1 ( < 1%)

1 (2%)

Ache

4 (2%)

0

0

Decreased cardiac output

3 (1%)

0

0

Arrhythmia

3 (1%)

0

0

Muscle rigidity

2 ( < 1%)

1 ( < 1%)

2 (5%)

Bradycardia

2 ( < 1%)

2 (1%)

0

Vomiting

1 ( < 1%)

2 (1%)

0

Premature ventricular beats

1 ( < 1%)

2 (1%)

0

Anemia

0

3 (2%)

0

Somnolence

0

0

1 (2%)

Fever

0

2 (1%)

0

*See Table 13 for recommended doses.

Table 8: Adverse Events Reported in 1% of Patients in the
Post-Study Drug Phase of Cardiac Surgery Studies at the Recommended Doses* of
ULTIVA (remifentanil)

Adverse Event

ULTIVA
n = 227

Fentanyl
n = 176

Sufentanil
n = 41

Nausea

90 (40%)

63 (36%)

16 (39%)

Vomiting

33 (15%)

26 (15%)

3 (7%)

Fever

30 (13%)

15 (9%)

0

Atrial fibrillation

27 (12%)

33 (19%)

4 (10%)

Constipation

20 (9%)

35 (20%)

3 (7%)

Pleural effusion

11 (5%)

2 (1%)

2 (5%)

Hypotension

8 (4%)

8 (5%)

1 (2%)

Tachycardia

9 (4%)

15 (9%)

0

Postoperative complication

10 (4%)

6 (3%)

2 (5%)

Oliguria

7 (3%)

7 (4%)

1 (2%)

Confusion

7 (3%)

10 (6%)

5 (12%)

Ache

6 (3%)

2 (1%)

0

Anxiety

6 (3%)

6 (3%)

0

Headache

6 (3%)

2 (1%)

0

Perioperative complication

5 (2%)

7 (4%)

1 (2%)

Anemia

5 (2%)

5 (3%)

1 (2%)

Agitation

5 (2%)

3 (2%)

1 (2%)

Diarrhea

5 (2%)

1 ( < 1%)

1 (2%)

Edema

4 (2%)

6 (3%)

0

Dizziness

4 (2%)

3 (2%)

1 (2%)

Postoperative infection

5 (2%)

7 (4%)

0

Hypoxia

4 (2%)

5 (3%)

0

Apnea

4 (2%)

1 ( < 1%)

1 (2%)

Hypertension

3 (1%)

3 (2%)

0

Shivering

3 (1%)

1 ( < 1%)

0

Heartburn

3 (1%)

3 (2%)

0

Atrial flutter

3 (1%)

1 ( < 1%)

0

Arrhythmia

3 (1%)

5 (3%)

0

Hallucinations

3 (1%)

3 (2%)

0

Pneumonia

3 (1%)

3 (2%)

1 (2%)

Pharyngitis

3 (1%)

1 ( < 1%)

1 (2%)

Decreased mental acuity

3 (1%)

1 ( < 1%)

0

Dyspnea

3 (1%)

1 ( < 1%)

0

Cough

3 (1%)

0

0

Decreased cardiac output

1 ( < 1%)

0

3 (7%)

Renal insufficiency

1 ( < 1%)

5 (3%)

0

Bradycardia

1 ( < 1%)

1 ( < 1%)

1 (2%)

Urine retention

2 ( < 1%)

3 (2%)

0

Cerebral infarction

2 ( < 1%)

2 (1%)

1 (2%)

Premature ventricular beats

2 ( < 1%)

3 (2%)

0

Cerebral ischemia

1 ( < 1%)

1 ( < 1%)

1 (2%)

Paresthesia

2 ( < 1%)

2 (1%)

0

Seizure

2 ( < 1%)

1 ( < 1%)

1 (2%)

Sleep disorder

1 ( < 1%)

1 ( < 1%)

1 (2%)

Bronchospasm

1 ( < 1%)

6 (3%)

0

Atelectasis

2 ( < 1%)

3 (2%)

0

Respiratory depression

2 ( < 1%)

3 (2%)

0

Pulmonary edema

1 ( < 1%)

2 (1%)

0

Respiratory distress

2 ( < 1%)

0

1 (2%)

Hyperkalemia

2 ( < 1%)

3 (2%)

0

Electrolyte disorder

0

3 (2%)

0

Chest congestion

0

3 (2%)

0

Hemoptysis

0

2 (1%)

0

Facial ptosis

0

2 (1%)

0

Hemorrhage

0

2 (1%)

0

Hematuria

0

1 ( < 1%)

1 (2%)

Visual disturbance(s)

0

1 ( < 1%)

1 (2%)

Hypokalemia

0

2 (1%)

0

Exacerbation of renal failure

0

0

1 (2%)

Blood in stool

0

0

1 (2%)

First degree heart block

0

0

1 (2%)

Pericarditis

0

0

1 (2%)

*See Table 13 for recommended doses.

Pediatrics: ULTIVA (remifentanil) has been studied in 342 pediatric patients in controlled
clinical trials for maintenance of general anesthesia. In the pediatric population
(birth to 12 years), the most commonly reported events were nausea, vomiting,
and shivering.

The frequencies of adverse events during general anesthesia with the recommended
doses of ULTIVA (remifentanil) are given in Table 9. Each patient was counted once for each
type of adverse event. There were no adverse events 1% for any treatment group
during the maintenance period in the pediatric patient general anesthesia studies.

Observed During Clinical Practice: In addition to adverse events reported
from clinical trials, the following events have been identified during post-approval
use of remifentanil in conjunction with one or more anesthetic agents in clinical
practice. Because they are reported voluntarily from a population of unknown
size, estimates of frequency cannot be made. These events have been chosen for
inclusion due to a combination of their seriousness, frequency of reporting,
or potential causal connection to remifentanil.